Novavax, Inc. today announced that top-line data from the Phase II dose-ranging clinical trial of its respiratory syncytial virus (RSV) vaccine candidate in women of childbearing age accomplished the trial's protocol-specified objectives and supports progression to the next stage of advanced clinical testing.

The trial represents an important step towards establishing the safety and immunogenicity of the vaccine candidate for use in a maternal immunization strategy. In such a strategy, the antibodies in vaccinated women can be expected to be naturally transferred to their infants in utero and thereby may confer passive protection at the earliest stage of life when these infants are extremely vulnerable to severe respiratory disease due to RSV.

This randomized, blinded, placebo-controlled Phase II clinical trial evaluated the safety and immunogenicity of two-dose levels of Novavax' RSV F protein nanoparticle vaccine candidate with and without aluminum phosphate (alum) as an adjuvant. The study enrolled 330 women of childbearing age who received either one or two intramuscular injections of a single-dose of vaccine or placebo, at study day 0 and day 28. Doses of 60 and 90 µg were tested, either with or without alum as an adjuvant. Safety and immunogenicity data for this clinical trial have been evaluated through day 56. Safety will continue to be evaluated over a total period of six months and immunogenicity for four months for each participant. The clinical trial is being conducted in collaboration with PATH, an international nonprofit organization that transforms global health through innovation. PATH committed funding of approximately $2 million to support this trial with the aim of advancing the development of an RSV vaccine to protect infants through maternal immunization in low-resource countries.

In this trial, the vaccine candidate was generally well-tolerated and the safety profile was similar to that observed previously in the Phase I clinical trial. The principal observation was transient mild to moderate injection site pain, predictably somewhat more frequent in the adjuvanted vaccine recipients. There were no clinically important differences in systemic adverse events between placebo and active vaccine recipients and no vaccine related SAEs. The most commonly reported systemic reactogenicity was comprised mainly of mild to moderate headache, fatigue and muscle ache, which are frequently noted after treatment by many vaccines. There were no differences in safety assessments across doses (60 and 90 µg) or worsening of reactogenicity with a second-dose. Laboratory testing did not reveal clinically significant changes in normal blood chemistries or hematology parameters.

The primary objectives of the study measured the difference in anti-F IgG elicited by the use of alum adjuvant, one versus two immunizations, and across doses (60 and 90 µg). The use of alum enhanced both the single and two-dose regimen anti-F IgG responses, with the greatest responses observed using a two-dose regimen. Peak geometric mean titers of anti-F IgG in the two-dose alum groups ranged from 12,000-14,000 representing a 13 to 16-fold rise, compared to a 6 to 10-fold rise in the non-alum groups. Minimal increases were observed by increasing the doses (60 to 90 µg). Peak geometric mean RSV A neutralizing antibodies in the alum groups ranged from log2 9.5-10.5, representing a 3.1 to 3.8-fold rise. Palivizumab-like antibody titers rose 8 to 9-fold, with four-fold rises in ≥92% of vaccinees in the two-dose alum adjuvanted vaccine groups. Overall, the immune responses observed in this Phase II clinical trial were similar to, or exceeded immune responses seen in the Phase I clinical trial using the Novavax nanoparticle vaccine.

"These results confirm that our RSV vaccine candidate has the potential to induce clinically useful immunity and has raised no safety concerns. The primary immunogenicity measures confirmed that the vaccine is a potent antigen and the aluminum phosphate adjuvant further enhanced the antibody responses. The results answered key questions regarding dose regimens and the use of aluminum phosphate as adjuvant," said Gregory Glenn M.D., Senior Vice President and Chief Medical Officer of Novavax. "With respect to secondary and exploratory objectives, we also observed that the vaccine induced peak neutralizing antibodies in excess of those seen in our Phase I trial, as well as reproducing palivizumab-like antibody responses. Neutralizing antibodies have been associated with decreased risk of hospitalization in infants and palivizumab is a licensed monoclonal antibody, marketed as Synagis®, that is used to prevent high-risk infant hospitalization due to RSV. The findings from this clinical trial indicate that our RSV F vaccine candidate has the potential to induce functional immune responses at levels that would be predicted to protect infants through maternal immunization. Overall, we are buoyed by these data and believe these findings warrant the pursuit of later-stage clinical trials."

Webcast and Conference Call

An audio webcast and conference call will be held with Novavax' senior management to discuss the results on April 3, 2013 at 10:00am EDT and available at www.novavax.com under Investor Info/Events. The dial-in number for the conference call is 1 (877) 212-6076 (U.S. or Canada) or 1 (707) 287-9331 (International). Webcast and telephone replays of the conference call will be available shortly after the completion of the call. To access the replay by telephone, dial 1 (855) 859-2056 (Domestic) or 1 (404) 537-3406 (International) and use passcode 30243955.

About RSV and Maternal Immunization

Maternal immunization is a strategy which can be used to protect infants from a variety of infectious diseases in the first months of life if enough protective antibodies can be transferred from mother to child. It is currently recommended by the US Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices for battling infant pertussis disease (whooping cough). Vaccine-induced maternal antibodies cross the placenta and often achieve concentrations in the fetus in excess of those seen in maternal sera. These naturally transferred antibodies are known to provide protection to the infant against many infectious diseases based on the exposure history of the mother, including protection against RSV in the first weeks of life. As the maternally derived antibody titers drop over time, infants become more susceptible to RSV disease. Maternal immunization for RSV is a potential clinical strategy aimed at boosting the level of antibodies transferred to infants and thereby extending the period over which they are protected. Field studies indicate that high concentrations of antibody in mothers due to natural exposure is correlated with lower RSV infection rates in newborns. RSV is the leading cause of hospitalization in the first months of life, an age at which implementation of complete active (direct) immunization is generally considered unlikely to succeed. More than half of US RSV related hospitalizations occur in infants three months of age and under. Globally, RSV is a common cause of childhood respiratory infection, with a disease burden of 64 million cases and causing approximately 160,000 deaths annually. Severe RSV disease results in 3.4 million hospital admissions per year globally and disproportionately affects infants below six months of age. A severe episode of RSV bronchiolitis can lead to recurrent bouts of reactive airway disease/asthma for many years after the initial event. RSV is a highly contagious virus that occurs as a predictable epidemic from late autumn through early spring in the US and other northern hemisphere regions, and can have two annual peaks or more in tropical climates. RSV disease burden in low-resource countries is significant, and available data indicate that the virus is responsible for a high proportion of childhood acute lower respiratory infection in these settings, particularly in the first few months of life. Currently, there is no approved RSV prophylactic vaccine available.